Transmission routes of HIV-1 gp120 from brain to lymphoid tissues

The blood-brain barrier (BBB) restricts the entry of antiviral agents into the CNS thereby facilitating the creation of a reservoir of HN that could p otentially reinfect peripheral tissues. We characterized the efflux from br ain of radioactively labeled viral coal HIV-1 gp120 (I-gp120) after intrace rebroventricular (i.c.v.) injection. The half-time disappearance rate of I- gp120 from brain was 12.6 min, which was faster than could be explained by the reabsorption of cerebrospinal fluid into blood but could not be explain ed by a saturable transporter. After i.c.v. injection, I-gp120 appeared in the serum and was sequestered by spleen and the cervical nodes, demonstrati ng a potential for virus within the CNS to reinfect peripheral tissues. How ever, the amount of I-gp120 appearing in serum was less than that expected based on the efflux rate, whereas uptake by the cervical nodes was much gre ater after i.c.v. than after i.v. injection of I-gp120. These findings were explained by drainage from the brain directly to the cervical lymph nodes through the brain's primitive lymphatic system. These lymphatics potentiall y provide a pathway through which CNS reservoirs of HIV-1 could directly re infect lymphoid tissue without being exposed to circulating antiviral agent s. (C) 1999 Elsevier Science B.V. All rights reserved.